"The U.S. Food and Drug Administration today approved Tivicay (dolutegravir), a new drug to treat HIV-1 infection.
Tivicay is an integrase strand transfer inhibitor that interferes with one of the enzymes necessary for HIV to multiply. "...
- Patient Information:
Details with Side Effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Serious and sometimes fatal hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Hematologic toxicity, including neutropenia and anemia [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Symptomatic myopathy [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Lactic acidosis and severe hepatomegaly with steatosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Acute exacerbations of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [WARNINGS AND PRECAUTIONS].
- Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine [see WARNINGS AND PRECAUTIONS].
- Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS].
- Fat redistribution [see WARNINGS AND PRECAUTIONS].
- Myocardial infarction [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a frequency greater than or equal to 5% during therapy with abacavir 300 mg twice daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily compared with indinavir 800 mg 3 times daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily from CNA3005 are listed in Table 1.
Table 1. Treatment-Emergent (All Causality) Adverse Reactions
of at Least Moderate Intensity (Grades 2-4, ≥ 5% Frequency) in Therapy-Naive
Adults (CNA3005) Through 48 Weeks of Treatment
|Adverse Reaction|| ZIAGEN plus
(n = 262)
| Indinavir plus
(n = 264)
|Malaise and fatigue||12%||12%|
|Nausea and vomiting||10%||10%|
|Fever and/or chills||6%||3%|
|Viral respiratory infections||5%||5%|
|Renal signs/symptoms||< 1%||5%|
|Pain (non-site-specific)||< 1%||5%|
Five subjects receiving abacavir in CNA3005 experienced worsening of pre-existing depression compared to none in the indinavir arm. The background rates of pre-existing depression were similar in the 2 treatment arms.
Laboratory Abnormalities: Laboratory abnormalities in CNA3005 are listed in Table 2.
Table 2. Treatment-Emergent Laboratory Abnormalities (Grades
3/4) in CNA3005
| Grade 3/4
|Number of Subjects by Treatment Group|
| ZIAGEN plus
(n = 262)
| Indinavir plus
(n = 264)
|Elevated CPK ( > 4 x ULN)||18(7%)||18(7%)|
|ALT( > 5.0xULN)||16 (6%)||16 (6%)|
|Neutropenia ( < 750/mm3)||13 (5%)||13 (5%)|
|Hypertriglyceridemia ( > 750 mg/dL)||5 (2%)||3 (1%)|
|Hyperamylasemia ( > 2.0 x ULN)||5 (2%)||1 ( < 1%)|
|Hyperglycemia ( > 13.9 mmol/L)||2 ( < 1%)||2 ( < 1%)|
|Anemia (Hgb ≤ 6.9 g/dL)||0 (0%)||3 (1%)|
| ULN = Upper limit of normal,
n = Number of subjects assessed.
Other Adverse Events: In addition to adverse reactions in Tables 1 and 2, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GOT.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of abacavir, lamivudine, and/or zidovudine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to abacavir, lamivudine and/or zidovudine.
Cardiovascular: Myocardial infarction.
Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.
There have also been reports of erythema multiforme with abacavir use.
Abacavir, Lamivudine, and/or Zidovudine:
Body as a Whole: Redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].
General: Vasculitis, weakness.
Psychiatric: Insomnia and other sleep disorders.
Respiratory: Abnormal breath sounds/wheezing.
Read the Trizivir (abacavir sulfate, lamivudine, and zidovudine) Side Effects Center for a complete guide to possible side effects
- No drug interaction trials have been conducted using TRIZIVIR Tablets [see CLINICAL PHARMACOLOGY].
Zidovudine: Stavudine: Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro.
Nucleoside Analogues Affecting DNA Replication: Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of zidovudine against HIV-1; concomitant use of such drugs should be avoided.
Zidovudine: Concomitant use of zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro.
Abacavir: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure [see CLINICAL PHARMACOLOGY].
Hematologic/Bone Marrow Suppressive/Cytotoxic Agents
Zidovudine: Coadministration of ganciclovir, interferon alfa, ribavirin, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.
Interferon- and Ribavirin-Based Regimens
Lamivudine: Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-1/HCV co-infected subjects, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected subjects receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
Abacavir: The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir. In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see CLINICAL PHARMACOLOGY]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.
Lamivudine: No change in dose of either drug is recommended [see CLINICAL PHARMACOLOGY]. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP.
Read the Trizivir Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/7/2012
This monograph has been modified to include the generic and brand name in many instances.
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